This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Google Scholar Articles by Juhaszova, M. Articles by Sollott, S. J. PubMed PubMed Citation Articles by Juhaszova, M. Articles by Sollott, S. J. Related Collections Other myocardial biology Cardiovascular Pharmacology Apoptosis Cell signalling/signal transduction Ischemic biology - basic studies Acute myocardial infarction Oxidant stress Receptor pharmacology

(Circulation Research. 2009;104:1240.)
© 2009 American Heart Association, Inc.

Review

Role of Glycogen Synthase Kinase-3β in Cardioprotection

Magdalena Juhaszova, Dmitry B. Zorov, Yael Yaniv, H. Bradley Nuss, Su Wang, Steven J. Sollott

From the Laboratory of Cardiovascular Science, Gerontology Research Center, National Institute on Aging, NIH, Baltimore, Md.

Correspondence to Steven J. Sollott, MD, Laboratory of Cardiovascular Science, Gerontology Research Center, Box 13, National Institute on Aging, NIH, 5600 Nathan Shock Dr, Baltimore, Maryland 21224-6825. E-mail sollotts{at}mail.nih.gov

Limitation of infarct size by ischemic/pharmacological pre- and postconditioning involves activation of a complex set of cell-signaling pathways. Multiple lines of evidence implicate the mitochondrial permeability transition pore (mPTP) as a key end effector of ischemic/pharmacological pre- and postconditioning. Increasing the ROS threshold for mPTP induction enhances the resistance of cardiomyocytes to oxidant stress and results in infarct size reduction. Here, we survey and synthesize the present knowledge about the role of glycogen synthase kinase (GSK)-3β in cardioprotection, including pre- and postconditioning. Activation of a wide spectrum of cardioprotective signaling pathways is associated with phosphorylation and inhibition of a discrete pool of GSK-3β relevant to mitochondrial signaling. Therefore, GSK-3β has emerged as the integration point of many of these pathways and plays a central role in transferring protective signals downstream to target(s) that act at or in proximity to the mPTP. Bcl-2 family proteins and mPTP-regulatory elements, such as adenine nucleotide translocator and cyclophilin D (possibly voltage-dependent anion channel), may be the functional downstream target(s) of GSK-3β. Gaining a better understanding of these interactions to control and prevent mPTP induction when appropriate will enable us to decrease the negative impact of the reperfusion-induced ROS burst on the fate of mitochondria and perhaps allow us to limit propagation of damage throughout and between cells and consequently, to better limit infarct size.

Key Words: mitochondria • ROS-induced ROS release • permeability transition pore

This article has been cited by other articles:

				L. Lacerda, S. Somers, L. H. Opie, and S. Lecour Ischaemic postconditioning protects against reperfusion injury via the SAFE pathway Cardiovasc Res, November 1, 2009; 84(2): 201 - 208. [Abstract] [Full Text] [PDF]

				J. Musiolik, P. van Caster, A. Skyschally, K. Boengler, P. Gres, R. Schulz, and G. Heusch Reduction of infarct size by gentle reperfusion without activation of reperfusion injury salvage kinases in pigs Cardiovasc Res, August 25, 2009; (2009) cvp271v2. [Abstract] [Full Text] [PDF]

				D. B. Zorov, M. Juhaszova, Y. Yaniv, H. B. Nuss, S. Wang, and S. J. Sollott Regulation and pharmacology of the mitochondrial permeability transition pore Cardiovasc Res, July 15, 2009; 83(2): 213 - 225. [Abstract] [Full Text] [PDF]